Changes in body temperature and vasopressin content of brain neurons, in pregnant and non-pregnant guinea pigs, during fevers produced by Poly I : Poly C

Abstract

The synthetic polyribonucleotide pyrogen Poly I:Poly C (800 micrograms.kg-1) was injected intramuscularly on alternate days into pregnant and non-pregnant female guinea pigs. Pregnant animals, close to term, had smaller fevers in response to the pyrogen than did non-pregnant animals. Repeated injections of the pyrogen caused sequentially smaller fevers for the first 3-4 injections, particularly in non-pregnant animals, and this appeared to be like the tolerance usually developed to repeated injections of endotoxin. Continued pyrogen injections then caused, in non-pregnant animals, fevers of increasing magnitude until the original fever levels were reached, whereas in pregnant guinea pigs the fever responses remained reduced until parturition. The development of tolerance was associated with an increase in immunoreactivity for arginine vasopressin (AVP) in some neurons in the medial part of the paraventricular nucleus, and in terminals in the lateral septum and amygdala similar to changes found in these areas at term of pregnancy. These observations raise the possibility that AVP in these regions may have a role in the development of tolerance to pyrogens, and further quantitative studies of the AVP content of, and release from, nerve terminals projecting to the limbic system seem warranted.

STAT3 and COX-2 activation in the guinea-pig brain during fever induced by the Toll-like receptor-3 agonist polyinosinic:polycytidylic acid

“…Therefore, polyinosinic:polycytidylic acid (PIPC), a synthetic analogue of doublestranded RNA, has been used as a model of viral infection (Fortier et al 2004;Traynor et al 2004). The properties of PIPC as a fever-inducing agent, a so-called "exogenous pyrogen", have repeatedly been demonstrated in rabbits (Absher and Stinebring 1969;Kimura et al 1994;Rotondo et al 1988;Soszynski et al 1991;Won and Lin 1988), rats (Chuang et al 1990;Fortier et al 2004;Ellis et al 2006), mice (Traynor et al 2004) and guinea-pigs (Cooper et al 1988;Li et al 2000;Voss et al 2006). Responses to PIPC in vivo and in vitro are mediated by activation of toll-like receptor (TLR)-3 signalling pathways (Alexopoulou et al 2001).…”

The viral mimic, polyinosinic:polycytidylic acid, induces fever in rats via an interleukin-1-dependent mechanism

“…Advantages of using poly I:C over live viruses include safety, convenience, but more importantly reproducibility and control over dose and time of administration of the immunological challenge. Similar to LPS, central or systemic administration of poly I:C results in the induction of the acute-phase reaction, fever, and sickness behaviors in a variety of species, including mice, rabbits, guinea pigs, and rhesus monkeys (11,16,19,20,48). Most studies examining the pyrogenic properties of poly I:C have been carried out in rabbits injected intravenously with low doses (2.5-50 g/kg) of poly I:C, which resulted in fevers of ϳ1°C in magnitude (20,22,46).…”

Alteration of the physiological responses to indomethacin by endotoxin tolerance in the rat: a possible role for central vasopressin.

“…This suggests that an endogenous factor may suppress fever in the tolerant animal. A role for central AVP in pyrogenic tolerance was hypothesized based upon increased immunocytochemical staining for ventral septal AVP in tolerant guinea-pigs (Cooper et al 1988) and the re-expression of the febrile response to LPS in tolerant rats subsequent to pharmacological blockade of ventral septal AVP receptors (Wilkinson & Kasting, 1990b). Indeed, local AVP release into push-pull perfusates is briefly enhanced in LPStreated tolerant rats (Wilkinson, Monda, Kasting & Pittman, 1992).…”